Salvage Chemotherapy in Patients with Previously Treated Thymic Carcinoma

SIMPLE SUMMARY: Thymic carcinoma is identified as thoracic neoplasm having low sensitivity to systemic chemotherapy. As first-line setting, platinum-based chemotherapy is administered, but, it is difficult to achieve long-term survival. Therefore, salvage chemotherapy is clinically considered as second or third line treatment. This study reviewed the therapeutic significance of several kinds of cytotoxic agents and molecular targeting drugs in patients with previously treated thymic carcinoma. The clinical trials of salvage chemotherapy in patients with thymic carcinoma are limited, and we cannot draw an optimal conclusion due to the small sample size. However, S-1, amrubicin, docetaxel, pemetrexed, and paclitaxel, sunitinib and lenvatinib yielded some efficacy to such patients. As S-1 and amrubicin are limited to Japan and East Asian, it remains unclear which regimens are better as second-line setting. Further investigation is warranted to establish the clinical evidence of salvage chemotherapy in advanced or metastatic thymic carcinoma by large-scale study. ABSTRACT: Thymic carcinoma is a rare neoplasm, and it is difficult to achieve complete remission with systemic chemotherapy. In advanced or recurrent thymic carcinoma, platinum-based chemotherapy is chosen as the first-line setting; however, it remains unclear which regimen is better to improve its outcome. It remains unknown whether salvage chemotherapy should be administered to patients with platinum-based chemotherapy-refractory thymic carcinoma. Currently, several clinical studies have investigated the efficacy of second-line settings for advanced thymic carcinoma. As cytotoxic agents, S-1, amrubicin, pemetrexed, docetaxel, paclitaxel, and gemcitabine have been reported as prospective phase II studies or retrospective studies. The overall response rates (ORRs) of S-1, amrubicin, and pemetrexed were 25–50%, 11–44.4%, and 9–10%, respectively. Molecular targeting drugs, such as sunitinib, everolimus, and lenvatinib, also provide clinical effectiveness with tolerability after the failure of platinum-based regimens. Based on the results of the prospective phase II study, the ORR, median progression-free survival, and median overall survival were 16.6% and 5.6 months, respectively, in everolimus, 26% and 7.2 months, respectively, in sunitinib, and 38% and 9.3 months, respectively, in lenvatinib. Although it is difficult to compare each study, lenvatinib appears to be better in increasing efficacy as a second-line setting. However, each study had a small sample size, which may have biased the results of their studies. Further investigation is warranted to elucidate the therapeutic significance of salvage chemotherapy in advanced thymic carcinoma in a large-scale study.